The Expression of T-Helper Associated Transcription Factors and Cytokine Genes in Pre-Eclampsia

Document Type: Original Article

Authors

1 Department of Immunology, Shiraz University of Medical Sciences, Shiraz,

2 Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Pre-eclampsia (PE) is known as a main factor contributing to
fetomaternal mortality, which might affect 2-8% of all pregnancies after the twentieth
week of gestation. The balance of T helper subsets is essential to sustain a normal
pregnancy and preventing fetomaternal complications. Objective: To investigate
differences in the levels of transcription factors and cytokine gene expression of
Th1/Th2/Th17/Treg subsets within decidual and chorionic layers of placentas from 15
PE-afflicted and 15 healthy Iranian women in their third trimester of pregnancy.
Methods: Using Quantitative real-time PCR (Q-PCR), The expression of T-BET,
GATA-3, ROR-ɣt, FOXP3, and cytokines, including IL-1, IL-6, TNF-α, IFN-γ, IL-4,
IL-31, IL-17, IL-23, TGF-β1, TGF-β2, TGF-β3, and IL-35 in the placenta were
compared at mRNA levels between groups. Results: FOXP3 and GATA-3 were
significantly down-regulated, while T-BET was up-regulated in PE deciduae compared
to the control group (p<0.0001, p<0.02, and p<0.01, respectively). Concerning the
chorionic samples, FOXP3 significantly decreased, while ROR-γt increased in the PE
placentas compared to the healthy ones (p<0.0006 and p<0.02, respectively). Besides,
most inflammatory cytokines were up-regulated, while anti-inflammatory cytokines
were down-regulated in the PE placentas. Additionally, TNF-α/IL-35, IFN-ɣ/IL-35, IL-
6/IL-35, and IL-23/IL-35 ratios were significantly higher (p<0.01) and IL-35/IL-17 ratio
was significantly lower (p<0.05) in the pre-eclamptic patients compared to the healthy
controls. Conclusion: Our results shed more light on the contribution of
Th1/Th2/Th17/Treg balance within placenta in the fate of a normal pregnancy.
Moreover, regulatory T cells and IL-35 seem to play a central role in the regulation of
all subsets.

Keywords